Cannabidiol (CBD), 600 mg/day orally for 5 to 12 days, inhibited hexobarbital metabolism in ten subjects. Hexobarbital oral clearance was 36% lower and apparent volume of distribution was 35% smaller, with no change in half-life during CBD. In four subjects who received intravenous and oral hexobarbital, systemic clearance was 36% lower while bioavailability was 10% greater during CBD. Hexobarbital increased fatigue and tremor, impaired eye-tracking performance, and altered the electroencephalogram. Hexobarbital effects were not affected by CBD. Inhibition of metabolism of other drugs should be considered when large amounts of CBD are taken or when CBD is used for therapy.